This application is for a new Adult AIDS Clinical Trials Unit (AACTU) in Pittsburgh as part of the Adult AIDS Clinical Trials Group (AACTG). The Pittsburgh Unit joined the AACTG in January 1997, by becoming a subunit of the Case Western Reserve University AACTU. Because of performance as a subunit and contributions to the scientific agenda of the AACTG, the Executive Committee recommended that the Pittsburgh Unit become a new AACTU in the next funding cycle (2000-2004). The Pittsburgh AACTU plans to enroll 360 patients into AACTG trials between 2000-2004 (60 patients year 1; 75 patients per year for years 2-5). This is well within the capacity of the Unit, which has over ten years of experience conducting NIH- and industry sponsored clinical trials in HIV-infected adults, including women and minorities. The establishment of an AACTU in Pittsburgh will permit several HIV researchers at the University of Pittsburgh to contribute to the scientific agenda of the AACTG. Under the leadership of the Principal Investigator, John W. Mellors, M.D., the research plan of the Pittsburgh Unit will concentrate on the following areas of the AACTG scientific agenda: (1) HIV Disease - identification of effective "rescue/salvage" therapies and evaluation of HIV drug resistance testing; (2) Infectious Complications - treatment and prophylaxis of opportunistic infections; (3) Immunology/immune-based Therapies - mechanisms of immune reconstitution and therapeutic vaccines; (4) Metabolic Complications - the effects of antiretroviral therapy on glucose metabolism, insulin sensitivity and body composition; (5) Neurologic Complications - neuropathogenesis of CNS HIV infection and the effects of treatment; (6) Longitudinal Linked Randomized Trials - virologic factors that predict drug failure; and (7) Pharmacology - distribution/interaction of antiretrovirals and interventions to enhance medication adherence.